Regulation of stem cells in the epidermis
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NESCI would be interested in funding / studentship opportunities for the following proposal.
NESCI are interested in industrial partners who may like to collaborate in one of these fields (for a CASE studentship or other awards), or in anyone who is interested in these areas of research (including other academic groups). For further details, please contact Helen Clamp from NESCI.
Project: Regulation of stem cells in the epidermis
Lead: Dr Julia Reichelt and Professor Maya Sieber-Blum
The epidermis is exposed to a wide range of physical force and keratinocytes are known to react to mechanical stress with increased proliferation causing epidermal thickening at sites of strain. Multipotent keratinocyte (KSC) and epidermal neural crest stem cells (EPI-NCSC) reside in the bulge of the hair follicle. The bulge is a stem cell niche within the epidermis of the hair follicle. KSC and EPI-NCSC are unique insofar as they are subjected to tensile forces from contractions of the arrector pili muscle (APM) which inserts at the bulge region. The physical proximity between these two types of stem cell with each other and with the APM suggests that KSC and EPI-NCSC communicate with each other and may be influenced or controlled by APM contraction.
Physical stimuli are sensed and integrated by distinct cell types, including stem cells, and depending on the context initiate diverse biological responses including cell proliferation, differentiation, developmental processes and regeneration. This PhD project will focus on studying the impact of APM contractility on the fate of bulge stem cells. To this end inducible transgenic reporter mice for KSC (Krt15CrePR;R26R) and EPI-NCSC (Wnt1-cre::R26R) (allowing tracking of both types of stem cell and their progeny) will be used to follow interaction between stem cell type and their response to mechanical stimulation by the APM. The major neurotransmitter at the APM is noradrenaline. Therefore the APM will be pharmacologically modulated in these mice using agents including sympathomimetic and sympatholytic drugs respectively. Migration, proliferation and differentiation of KSC and EPI-NCSC will be analysed on skin sections and in whole mount preparations, using BrdU labelling and keratinocyte and melanocyte differentiation markers. Moreover norepinephrine transporter knockout mice (NETKO), which are deficient in norepinephrine reuptake from the synaptic cleft, with hair loss and wound healing impairment, will be used to study the fate of epidermal stem cells residing in the bulge under normal conditions and in wound healing situations. In addition, the response of co-cultured (GFP-labelled) KSC and EPI-NCSC to mechanical stretch will be studied using the Flexcell system.
Results from these studies will provide important biological insight into the regulation of stem cells in the epidermis.
